Regulation of Area Identity in the Mammalian Neocortex by
            <i>Emx2</i>
            and
            <i>Pax6</i>

Bishop, Kathie M.; Goudreau, Guy; O’Leary, Dennis D.M.

doi:10.1126/science.288.5464.344

Cited by 556 publications

(479 citation statements)

References 34 publications

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“…1G). Notably, this transcriptional profile mirrors the Emx2 high caudodorsal to low rostroventral expression gradient (Bishop et al, 2000;Mallamaci et al, 2000b), although Arx domain seems to be nested into the Emx2-positive territory and, thus, covering a smaller telencephalic territory.…”

Section: Resultsmentioning

confidence: 75%

Mouse orthologue of ARX, a gene mutated in several X‐linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons

Colombo¹,

Galli²,

Cossu³

et al. 2004

Developmental Dynamics

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Section: Resultsmentioning

confidence: 75%

Mouse orthologue of ARX, a gene mutated in several X‐linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons

Colombo¹,

Galli²,

Cossu³

et al. 2004

Developmental Dynamics

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“…In this experimental session (EXP3), we used embryonic neural precursors from þ/null heterozygous embryos, as full inactivation of Foxg1 or Emx2, deeply impacting on telencephalic and pallial regionalization [16,35,36,48], would complicate subsequent interpretation of results.…”

Section: Histogenetic Consequences Of Reduced Emx2 and Foxg1 Dosagesmentioning

confidence: 99%

“…It is implicated in several key aspects of cortical development, including cortico-cerebral field specification [34], its areal patterning [34][35][36], and neocortical lamination [37,38]. As for control of precursor kinetics, profiling of Emx2-loss of function (LOF) and Emx2-gain of function (GOF) precursor cells showed that Emx2, although not affecting the lineage fate choice, seemed to alternatively promote precursors self-renewal or their neuronal differentiation, depending on the experimental context [16,[39][40][41][42].…”

Section: Introductionmentioning

confidence: 99%

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

et al. 2010

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Neural stem cells (NSCs) give rise to all cell types forming the cortex: neurons, astrocytes, and oligodendrocytes. The transition from the former to the latter ones takes place via lineage-restricted progenitors in a highly regulated way. This process is mastered by large sets of genes, among which some implicated in central nervous system pattern formation. The aim of this study was to disentangle the kinetic and histogenetic roles exerted by two of these genes, Emx2 and Foxg1, in cortico-cerebral precursors. For this purpose, we set up a new integrated in vitro assay design. Embryonic cortical progenitors were transduced with lentiviral vectors driving overexpression of Emx2 and Foxg1 in NSCs and neuronal progenitors. Cells belonging to different neuronogenic and gliogenic compartments were labeled by spectrally distinguishable fluoroproteins driven by cell type-specific promoters and by cell type-specific antibodies and were scored via multiplex cytofluorometry and immunocytofluorescence. A detailed picture of Emx2 and Foxg1 activities in cortico-cerebral histogenesis resulted from this study. Unexpectedly, we found that both genes inhibit gliogenesis and promote neuronogenesis, through distinct mechanisms, and Foxg1 also dramatically stimulates neurite outgrowth. Remarkably, such activities, alone or combined, may be exploited to ameliorate the neuronal output obtainable from neural cultures, for purposes of cell-based brain repair. STEM CELLS

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“…Establishing a relationship between area size and behavioral performance could be predictive for behavioral differences between individuals and provide insight into the functional importance of cortical areas (2). These relationships could also provide insights into developmental cognitive disorders (10) and the potential for aberrant behavior due to polymorphisms that influence the expression of regulatory genes that control area patterning (11).Area size is controlled in part by transcription factors, including the homeodomain protein EMX2 expressed by cortical progenitors, that specify during embryonic development the area identities of cortical progenitors and their neuronal progeny (12)(13)(14). Analyses of nestin-Emx2 transgenic (ne-Emx2) mice and heterozygous Emx2 knockout (Emx2ϩ/Ϫ) mice, which have increased or decreased levels of Emx2 expression in cortical progenitors, respectively, show opposing changes in sizes of S1 and motor areas in mature mice (14).…”

mentioning

confidence: 99%

Cortical area size dictates performance at modality-specific behaviors

Leingärtner

Thuret

Kroll

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The mammalian neocortex is organized into unique areas that serve functions such as sensory perception and modality-specific behaviors. The sizes of primary cortical areas vary across species, and also within a species, raising the question of whether area size dictates behavioral performance. We show that adult mice genetically engineered to overexpress the transcription factor EMX2 in embryonic cortical progenitor cells, resulting in reductions in sizes of somatosensory and motor areas, exhibit significant deficiencies at tactile and motor behaviors. Even increasing the size of sensorimotor areas by decreasing cortical EMX2 levels can lead to diminished sensorimotor behaviors. Genetic crosses that retain ectopic Emx2 transgene expression subcortically but restore cortical Emx2 expression to wild-type levels also restore cortical areas to wild-type sizes and in parallel restore tactile and motor behaviors to wild-type performance. These findings show that area size can dictate performance at modality-specific behaviors and suggest that areas have an optimal size, influenced by parameters of its neural system, for maximum behavioral performance. This study underscores the importance of establishing during embryonic development appropriate levels of regulatory proteins that determine area sizes, thereby influencing behavior later in life.cortex ͉ EMX2 ͉ sensorimotor performance ͉ cortical area patterning ͉ somatosensory cortex T he mammalian neocortex is tangentially organized into areas that serve unique functions such as sensory perception and modality-specific behaviors. In humans, the primary areas, motor (M1), somatosensory (S1), and visual (V1), vary Ϸ2-fold in size in a smooth continuum (1-5). In mice, the sizes of V1 and the S1 barrelfield are very consistent within inbred strains of mice, but their mean sizes can differ between some inbred strains of mice (6).These observations raise the question of whether the size of a cortical area influences behavioral performance. Normal humans exhibit significant differences in proficiency at visual psychophysical tasks (7), but these differences have not been correlated to differences in area size. Complementing these findings are studies of adult cortical plasticity. For example, repetitive use of a digit, or microstimulation of its cortical representation, results in an enlarged functional representation in M1 and S1 resulting in an increased overlap with functional representations of adjacent digits. These enlargements, which are evident physiologically but not anatomically, do not extend across area borders, do not increase area size, and have not been shown to affect systems-level behavior (8, 9).Here we address whether differences in cortical area size influence modality-specific behaviors in adults by using genetic manipulations that act during embryonic development to alter cortical area size in a consistent, reproducible manner. Establishing a relationship between area size and behavioral performance could be predictive for behavioral differences between ...

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Regulation of Area Identity in the Mammalian Neocortex by Emx2 and Pax6

Cited by 556 publications

References 34 publications

Mouse orthologue of ARX, a gene mutated in several X‐linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons

Mouse orthologue of ARX, a gene mutated in several X‐linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

Cortical area size dictates performance at modality-specific behaviors

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